Article

Biological Trace Element Research

, Volume 131, Issue 3, pp 229-244

Selenoprotein W Modulates Control of Cell Cycle Entry

  • Wayne Chris HawkesAffiliated withUSDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis Email author 
  • , Thomas T. Y. WangAffiliated withUSDA Agricultural Research Service, Beltsville Human Nutrition Research Center
  • , Zeynep AlkanAffiliated withUSDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis
  • , B. Diane RichterAffiliated withUSDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis
  • , Kevin DawsonAffiliated withNCMHD Center for Excellence in Nutritional Genomics, University of California at Davis

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Abstract

The present study was conducted to identify targets of selenium (Se) provided to cultured human cells in physiologically relevant doses and forms. Breast and prostate epithelial cells were supplemented with Se provided as 100 nM sodium selenite or high-Se serum and gene expression was profiled with DNA microarrays. Pure sodium selenite affected expression of 560 genes in MCF-10A breast cells, including 60 associated with the cell cycle (p = 2.8 × 10−16). Selenoprotein W (SEPW1) was the only selenoprotein messenger RNA (mRNA) increased by both sodium selenite (specific) and high-Se serum (physiologic). SEPW1 small interfering RNA inhibited G1-phase progression and increased G1-phase gene transcripts, while decreasing S-phase and G2/M-phase gene transcripts, indicating the cell cycle was interrupted at the G1/S transition. SEPW1 mRNA levels were maximal during G1-phase, dropped after the G1/S transition and increased again after G2/M-phase. SEPW1-underexpressing prostate cells had increased mRNA for BCL2, which can induce a G1 arrest, and decreased mRNA for RBBP8 and KPNA2, which modulate the Rb/p53 checkpoint pathway. These results suggest that SEPW1 and the G1/S transition are physiological targets of Se in breast and prostate epithelial cells.

Keywords

Selenium Cancer G1/S transition Cell cycle entry Nutrition Chemoprevention